Metabolism of norepinephrine in vitro by dog pulmonary arterial endothelium.

The importance of endothelial cells in the removal of norepinephrine from synaptic clefts in dog pulmonary artery was studied. Strips of artery cut helically were denuded of endothelium by gently stroking the intimal surface with a wooden applicator stick or were studied with endothelium intact. All strips were prelabeled in L-[3H]norepinephrine (2 X 10(-7) M) and mounted for superfusion. Superfusate was collected continuously before, during, and after electrical stimulation (10 V, 2 ms, 2 Hz). Measurements were made of the amounts of [3H]norepinephrine and its metabolites in superfusate and in tissue. These studies have established that 3,4-dihydroxyphenylglycol is of neuronal origin and O-methylated metabolites are of extraneuronal origin. The formation of extraneuronal metabolites in smooth muscle and endothelium was examined by either blocking uptake of norepinephrine into each, in turn, or by combining blockade of uptakes with the elimination of access of norepinephrine to endothelial tissue by completely removing it. Electrical stimulation elicited the overflow of large amounts of norepinephrine, 3,4-dihydroxyphenylglycol, and O-methylated metabolites into superfusate in strips with intact endothelium; in strips denuded of endothelium there were striking decreases in the amounts of O-methylated metabolites produced. These studies show that pulmonary arterial endothelium participates in the extraneuronal metabolism of norepinephrine released by sympathetic nerve stimulation.